Procaine urea salicylate and process of obtaining the same



Patented Feb. 27, 1951 T UNITED STATES PATENT OFFICE PROCAINE UREA SALICYLATE AND PROCESS OF OBTAINING THE SAME Ralph N. Lulek, Rosebank, N. Y., assignor to Heyden Chemical Corporation, New York, N. Y., a corporation of Delaware No- Drawing. Original application December 8,

1948, Serial No. 64,241. Divided and this application. October 20, 1949, Serial No. 122,601

7' Claims. (01. 260472) 2 My invention relates particularly to derivatives which is very soluble in water and used as a subof the drug procaine, or novocaine, and especially stitute for cocaine and as a local anaesthetic, procaine urea, (C13H19O2N2)2CO, and procaine Martin Organic Chemistry, 3rd ed., 1917, page urea salicylate obtained therefrom and the proc- 604, Appleton & Company, New York, Thorpe, App. ess of producing the same. 5 Chem., v. III, 1916, page I18, is passed 100, grams This pp on i a d v s n Of y pplication of phosgene. The temperature of the mixture is upon Procaine Derivatives, Ser. No. 64,241, filed preferably held between and C. during the December 8, 1948, o e t umbe ,848. addition. Then the mixture is chilled to 15 0.

An ject of my invention is produce Such and filtered, and the solid product obtained is rederivatives, also especially to obtained modified 0 crystallized three times from 0% strength t forms of the well known drug novocaine, such as anol, and once from 9 strength t r t hiihert" unknown pmcaine urea salicylate, yield 50% of the theoretical amount of procaine (C13H1902N2) flown-1 09 urea. The product obtained melts at about which may be obtained from procaine urea, 15 (C13H19O2N2) 200, the said procaine urea salicyl- It W111 be rstood however that the properate being a therapeutic product used in the treatmom of pyndme. and e.thy1 q can Vary ment of ulcers comprising a modified form of the through any deslred i hmlts' Instead of said novocaine providing a source of the salicylic ethyl acetate I may Substltute m smtable acid used in treating ulcers, Therapeutic Materia 0 Solvent as for Instance acetone lsopropylacetate' Medica and Pharmacy, Potter, 13th ed., 1917, page eta Also the temperature may be Varied 862, Blakistonis Sons & C0 Phila" Pa The tween 15 and C., as desired, for the reaction. object is, also to provide new chemical compounds Instead of pyridine I may Substitute for example and to advance the art accordingly. quin01ine 01 dimethyl n While my invention may have many different 5 In moklng procaine a a at w h may embodiments and may be carried out in many difbe expressed s ferent ways, for the purpose of illustration I have described hereinafter only' certain examples (C13H1902N2)2C0(C7H603)2 thereof. or structurally as i i i i i (C2Hu)2N-CH2CH2O CC NC-NCOCH2CE/I;N(\C2Ht)a H/ o o H OH r o11 For example, to make procaine urea, I may proceed as follows, for example:

A solution of 13.8 grams of salicylic acid in 50 (C13H1902N2)2Co grams of ethanol, having a strength of is which may be expressed a 4 added to an ethanol solution of 25 grams of said 0 o o II H I H II (CzHQzNOHrCHzOC -N-C--N COCH2CH2N(C2H5)2 which is di-(e-diethylamino) ethyl ester of 4,4'- pro aine ur a c ntaining 30 ram of ha ol of dicarboxy diphenyl urea or 4,4'-di-(p-diethyl- 95% strength. When the alcohol has been reamino) carbethoxy diphenyl urea, and which is 50 moved by distillation the oil remaining solidifies used in producing the procaine urea salicylate, I on standing- ThiS So is recrystallized from may proceed as follows; ether-methanol comprising 200 cc. of ether and Intoamixture ofl liter ofatertiary base, such 200 of methanol and then air dried- The as ridin 1 lit of ethyl t t d 512 grams yield of procaine urea salicylate is 91.5%, based of procaine hydrochloride t t i t ay n0v0 55 on the procaine urea originally present. It melts caine hydrochloride at about C- The proportions of the ethanol as above can be varied within wide limits, as desired. Also, instead of ethanol I may substitute other alco- 3 V hols, such asisopropanol, n-propanol, etc., and instead of the ether-methanol solution I may substitute substantially any other ether-alcohol mixture as a solvent.

While I have described my invention above in detail it will be understood that the same may be varied without departing from the spirit of my salicylic acid with procaine urea to produce pro caine urea salicylate.

3. The process whichcomprises reacting upon salicylic acid with procaine urea in the presence of an alcohol to produce'procaine urea salicylate, then dissolving the product in ether and methanol and crystallizing the same therefrom. e

4; The process which comprises reacting upon salicylic acid with procaine urea in the presence same therefrom.

-of ethanol to produce procaine urea salicylate,

then dissolving the product in ether and methanol and crystallizing the same therefrom.

5. The process which comprises reacting in 2:1 molar proportions upon salicylic acid with procaine urea to produce procaine urea salicylate.

6. The process which comprises reacting in 2:1 molar proportions upon salicylic acid with procaine urea in the presence of an alcohol to produce procaine urea salicylate, then dissolving the product in ether and methanol and crystallizing the same therefrom.

7. The process which comprises reacting in 2:1 molar proportions upon salicylic acid with procaine urea in the presence of ethanol to produce procaine urea salicylate", then dissolving the product inether and methanol and crystallizing the RALPH N. LULEK.

No references cited. 

1. AS A CHEMICAL COMPOUND, PROCAINE UREA SALICYLATE HAVING A MELTING POINT OF ABOUT 102* TO 105* C. 